Sulfuric Acid → HCID 86751652, compound

HRID 2294717Notes

Reaction equation

HRID 2294717 reaction equation
[CH2:1]([O:8][C:9](=[O:16])[CH2:10][C@@H:11]([C:13]([OH:15])=[O:14])[NH2:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[CH3:22][C:23](=[CH2:25])[CH3:24].[C:26]([NH:33][CH2:34][C:35]([OH:37])=O)([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>O1CCOCC1.CN(C)C=O.CCOCC>[C:29]([O:28][C:26]([NH:33][CH2:34][C:35]([NH:12][C@H:11]([C:13]([O:15][C:23]([CH3:25])([CH3:24])[CH3:22])=[O:14])[CH2:10][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:16])=[O:37])=[O:27])([CH3:30])([CH3:31])[CH3:32]

Participants

10

Reactant 6

HCID 1118Sulfuric AcidHCID 79724-MethylmorpholineHCID 8255IsobutyleneHCID 78288N-(tert-butoxycarbonyl)glycineHCID 1011864-(Phenylmethyl) hydrogen L-aspartateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 86751652HCID 86751652, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 12 g (54 mmol) of L-aspartic acid 4-benzyl ester, 10 ml of concentrated sulphuric acid and 100 ml of liquid isobutylene in 100 ml of dry dioxan is stirred at room temperature overnight in a pressure flask. Thereafter, the solution is added dropwise to 500 ml of ice-cold 1N sodium hydroxide solution. The aqueous phase is extracted three times with ether. The combined organic phases are dried over sodium sulphate and evaporated. The viscous oil obtained (13.85 g) is dissolved in 250 ml of dry dimethylformamide and stirred at room temperature for 4 hours with 9.55 g (54.5 mmol) of Boc-glycine, 20.7 g (54.5 mmol) of HBTU and 6 ml (54.5 mmol) of N-methylmorpholine. Subsequently, the reaction mixture is evaporated in a high vacuum and the residue obtained is taken up in ether. The organic phase is washed with 5% sodium carbonate solution and water, thereafter dried over sodium sulphate and evaporated under reduced pressure. The oily residue is chromatographed on silica gel using a 1:1 mixture of hexane and ether as the eluent. There is obtained 4-benzyl 1-tert-butyl N-[(1-tert-butoxyformamido)acetyl]-L-aspartate as a viscous oil; MS: 437 (M+H)+.

Workup

  1. extractionThe aqueous phase is extracted three times with ether
  2. dry with materialThe combined organic phases are dried over sodium sulphate
  3. customevaporated
  4. customThe viscous oil obtained (13.85 g)
  5. customSubsequently, the reaction mixture is evaporated in a high vacuum
  6. customthe residue obtained
  7. washThe organic phase is washed with 5% sodium carbonate solution and water
  8. dry with materialdried over sodium sulphate
  9. customevaporated under reduced pressure
  10. customThe oily residue is chromatographed on silica gel using
  11. additiona 1:1 mixture of hexane and ether as the eluent

Sources & evidence

ORD record
ord-624fb2a7306d42b9985fe5474861af30
Source dataset
uspto-grants-1997_11
Patent number
US05688946

Reaction notes

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